Ultra-high-purity silica microspheres recently were introduced primarily for analytical high-performance liquid chromatography (HPLC). However, these materials are expensive and are available only in limited configurations. The aim of this proposal is to explore new methods for preparing strong, ultra-high-purity silica microspheres (or microspheroids) of lower cost in a variety of configurations (particle size, pore size, etc.) for various separation processes. The availability of these ultra-pure, less-acidic silica particles would permit superior separations of sensitive materials, particularly those of biological origins. Such particles also would produce higher separation yields with fewer problems than are associated with currently-available silicas. Porous silica microspheroids in the 2-20 mu m range are useful for analytical HPLC separations. Similar 10-50 mu m particles are well suited for preparative HPLC, and as support media for high-performance solid-phase extraction and affinity chromatography. Methods also will be sought to prepare superficially porous microspheres to permit very fast separations of macromolecules with conventional HPLC apparatus, techniques and column-packing methods. The purpose of Phase I is to develop practical preparation methods to permit ultimate commercialization of the porous silica particles of this proposal.